It is now generally recognized that the thymus gland controls the development and maintenance of the immune system by both endocrine and cellular components which contribute to initiating and maintaining the ability to combat invasions by pathogens or growth of neoplastic tissue and in preventing autoimmune disease. The proposed studies are based upon the previous isolation and partial purification of thymosin fraction 5, a family of polypeptides isolated from calf thymus, and the demonstration that these polypeptides can partially or fully reconstitute immune function in thymic deprived animals and in humans with a number of primary immunodeficiency diseases or cancer. Of major potential importance to the goals of the National Cancer Program in the cancer treatment area is the recent completion of the first Phase II randomized trials of Dr. Chretien and colleagues at the National Cancer Institute in Bethesda, showing that thymosin when given in conjunction with chemotherapy for small cell carcinoma of the lung significantly prolongs survival compared to patients receiving chemotherapy alone. This is the first successful prospective randomized trial of immunotherapy in small cell carcinoma of the lung. The research proposed in this study has the following objectives: (1) to chemically characterize and determine the amino acid sequences of the peptide components of thymosin fraction 5 that have immunoreconstitutive effects, (2) to develop and standardize large-scale procedures for the production of the biologically active peptides in fraction 5 adequate for human use, and (3) to determine in animal models the efficacy of these peptides in alleviating specific immunological defects.